2-Amino-5-bromopyridine → Methyl 4-oxo-4-[[5-(3-pyridyl)-2-pyridyl]amino]butanoate

HRID 526005Notes

Reaction equation

HRID 526005 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:6][CH:7]=1.Br[C:18]1[CH:19]=[CH:20][C:21](N)=[N:22][CH:23]=1.N1C=CC=C([Sn](CCCC)(CCCC)CCCC)C=1>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:16]=[C:9]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([C:20]2[CH:21]=[N:22][CH:23]=[CH:18][CH:19]=2)=[CH:7][N:6]=1)[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]

Participants

6

Reactant 3

HCID 706222-Amino-5-bromopyridineHCID 1506825Methyl 4-[(5-bromopyridin-2-yl)amino]-4-oxobutanoateHCID 34838483-(Tributylstannyl)pyridine

Product 1

HCID 89444420Methyl 4-oxo-4-[[5-(3-pyridyl)-2-pyridyl]amino]butanoateYield 26%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

Methyl 4-[(5-bromo-2-pyridyl)amino]-4-oxo-butanoate (Commercially available or prepared as described in example II using as starting material the commercially available: 5-bromo-2-aminopyridine, 200 mg, 0.697 mmol) was dissolved in toluene in a microwave vial and 3-pyridyltributylstannane (0.836 mmol, 0.290 mL) and tetrakis(triphenylphosphine) palladium(0) (0.069 mmol) were added. Argon was bubbling through the mixture for ca. 5 min and the vial was heated under microwave irradiations for 10 min at 150° C. The solvent was evaporated and the residue was diluted with acetonitrile, washed with cyclohexane (2×) and evaporated. The product was purified by flash chromatography (RF-machine, AcOEt/cyclohexane: 0/100→100/0) to give methyl 4-oxo-4-[[5-(3-pyridyl)-2-pyridyl]amino]butanoate (compound A82) (0.051 g, 26% Yield). LC-MS (Method F) RT 0.50, 286 (M+H+). Compound A83, A84 and A85 from table A were prepared by the same method using the corresponding coupling reagent.

Workup

  1. additionwere added
  2. customArgon was bubbling through the mixture for ca. 5 min
  3. customThe solvent was evaporated
  4. additionthe residue was diluted with acetonitrile
  5. washwashed with cyclohexane (2×)
  6. customevaporated
  7. customThe product was purified by flash chromatography (RF-machine, AcOEt/cyclohexane: 0/100→100/0)

Sources & evidence

ORD record
ord-9e24008c48f541cb90bcf74831b04a1c
Source dataset
uspto-grants-2016_05
Patent number
US09345244B2

Reaction notes

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